Riemann Zeta
Bluelighter
- Joined
- Apr 21, 2004
- Messages
- 1,655
Dextromethorphan is one of the most fascinating drugs I have ever encountered--it has a bewildering array of psychical/phenomenological effects, including dissociative, empathoogenic, stimulant, depressant, psychedelic, euphoric and dysphoric qualities. In myself, dextromethorphan often functions as a 'bittersweet emotional amplifier,' creating profound feelings of both happiness/contentment and feelings of nostalgia/sentimentality. Perhaps most interesting is the dose-dependent and inter-subject variance of the effects of dextromethorphan. My wife, for example, has a similar response to my own (at lower doses), albeit with notable nausea and motion-sickness; yet my mates usually only experience spatiotemporal distortion and psychedelic effects (at any dose). In most individuals I know, low doses are often empathogenic and stimulating, whereas high doses are either fully dissociative (akin to ketamine) or psychedelic.
Obviously, it is well known that dextromethorphan and its O-desmethyl metabolite dextrophan are MK801-esque noncompetitive NMDA receptor antagonists, with Ki values of 405.2 and 2913 nM, respectively (Sun & Wessinger, 2004). This makes sense considering the PCP/ketamine-like efffects. However, little is known about the other effects of the drug. Like PCP and SKF-10047, dextromethorphan (and dextrophan) are potent sigma-receptor agonists. No really knows what the sigma receptor does, but many think that it is an auxiliary subunit to the voltage-gated Kv1.4/1.5 potassium channel (Ayudar et al, 2002). It is unknown whether or not the sigma receptor plays a large role in the effects of dextromethorphan or PCP, but other sigma ligands appear to have some limited psychedelic properties.
I am most interested in the interactions that dextromethorphan (and dextrophan) may have with the dopaminergic and/or serotonergic systems. Coadministration of MDA/MDMA/MDEA or d-fenfluramine with dextromethorphan results in 5-HT syndrome. Thus, dextromethorphan is likely also a 5-HT reuptake inhibitor or 5-HT releaser (do other NMDA antagonists/sigma ligands cause 5-HT syndrome?). Also, many people claim dextromethorphan is a dopamine reuptake inhibitor. In fact, dextromethorphan does indeed have some in vitro affinity for the DAT, but this claim is sketchy at best (it has never been tested in vivo). So, what does everyone think?
Obviously, it is well known that dextromethorphan and its O-desmethyl metabolite dextrophan are MK801-esque noncompetitive NMDA receptor antagonists, with Ki values of 405.2 and 2913 nM, respectively (Sun & Wessinger, 2004). This makes sense considering the PCP/ketamine-like efffects. However, little is known about the other effects of the drug. Like PCP and SKF-10047, dextromethorphan (and dextrophan) are potent sigma-receptor agonists. No really knows what the sigma receptor does, but many think that it is an auxiliary subunit to the voltage-gated Kv1.4/1.5 potassium channel (Ayudar et al, 2002). It is unknown whether or not the sigma receptor plays a large role in the effects of dextromethorphan or PCP, but other sigma ligands appear to have some limited psychedelic properties.
I am most interested in the interactions that dextromethorphan (and dextrophan) may have with the dopaminergic and/or serotonergic systems. Coadministration of MDA/MDMA/MDEA or d-fenfluramine with dextromethorphan results in 5-HT syndrome. Thus, dextromethorphan is likely also a 5-HT reuptake inhibitor or 5-HT releaser (do other NMDA antagonists/sigma ligands cause 5-HT syndrome?). Also, many people claim dextromethorphan is a dopamine reuptake inhibitor. In fact, dextromethorphan does indeed have some in vitro affinity for the DAT, but this claim is sketchy at best (it has never been tested in vivo). So, what does everyone think?
